Autoinjector

ABSTRACT

An autoinjector includes a case adapted to hold a medicament container having a needle, a needle shroud telescopically coupled to the case, and a plunger rotationally and slidably disposed in the case. The needle shroud is movable between a first extended position relative to the case in which the needle is covered and a retracted position relative to the case in which the needle is exposed. The plunger is rotatable relative to the case between a first rotational position in which the plunger is engaged to the case and a second rotational position in which the plunger disengages the case. The needle shroud is operably coupled to the plunger. When the needle shroud translates from the first extended position to the retracted position, the plunger rotates from the first rotational position to the second rotational position.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/521,266, filed Jul. 24, 2019, which is a continuation of U.S. patentapplication Ser. No. 14/903,359, filed Jan. 7, 2016, now U.S. Pat. No.10,398,848, which is a U.S. national stage application under 35 USC §371 of International Application No. PCT/EP2014/064427, filed on Jul. 7,2014, which claims priority to European Patent Application No.13175664.5, filed on Jul. 9, 2013, the entire contents of which areincorporated herein by reference.

TECHNICAL FIELD

The invention relates to an autoinjector.

BACKGROUND

Administering an injection is a process which presents a number of risksand challenges for users and healthcare professionals, both mental andphysical. Injection devices typically fall into two categories—manualdevices and autoinjectors. In a conventional manual device, manual forceis required to drive a medicament through a needle. This is typicallydone by some form of button /plunger that has to be continuously pressedduring the injection. There are numerous disadvantages associated withthis approach. For example, if the button/plunger is releasedprematurely, the injection will stop and may not deliver an intendeddose. Further, the force required to push the button/plunger may be toohigh (e.g., if the user is elderly or a child). And, aligning theinjection device, administering the injection and keeping the injectiondevice still during the injection may require dexterity which somepatients (e.g., elderly patients, children, arthritic patients, etc.)may not have.

Autoinjector devices aim to make self-injection easier for patients. Aconventional autoinjector may provide the force for administering theinjection by a spring, and trigger button or other mechanism may be usedto activate the injection. Autoinjectors may be single-use or reusabledevices.

There remains a need for an improved autoinjector.

SUMMARY

It is an object of the present invention to provide an improvedautoinjector.

In an exemplary embodiment, an autoinjector according to the presentinvention comprises a case adapted to hold a medicament container havinga needle, a needle shroud telescopically coupled to the case and movablebetween a first extended position relative to the case in which theneedle is covered and a retracted position relative to the case in whichthe needle is exposed, and a plunger rotationally and slidably disposedin the case. The plunger is rotatable relative to the case between afirst rotational position in which the plunger is engaged to the caseand a second rotational position in which the plunger disengages thecase. The needle shroud is operably coupled to the plunger. When theneedle shroud translates from the first extended position to theretracted position, the plunger rotates from the first rotationalposition to the second rotational position.

In an exemplary embodiment, the needle shroud is movable from theretracted position to a second extended position relative to the case inwhich the needle is covered and the needle shroud cannot translaterelative to the case.

In an exemplary embodiment, the autoinjector further comprises a capremovably coupled to the case. The cap may include an element adapted toengage a protective needle sheath removably disposed on the needle. Thecap may include at least one compliant beam adapted to releasably engageat least one radial aperture in the needle shroud. When the cap iscoupled to the case the at least one compliant beam engages the at leastone radial aperture in the needle shroud and radially abuts the case.When the cap is removed from the case, the at least one compliant beamdisengages the at least one radial aperture in the needle shroud and nolonger radially abuts the case.

In an exemplary embodiment, the autoinjector further comprises a shroudspring biasing the needle shroud in a distal direction relative to thecase.

In an exemplary embodiment, the autoinjector further comprises a drivespring biasing the plunger in a distal direction relative to the case.The plunger translates relative to the case under force of the drivespring when the plunger is in the second rotational position and theneedle shroud is in the retracted position. The plunger may be at leastpartially hollow and the drive spring may be at least partially disposedwithin the plunger.

In an exemplary embodiment, the needle shroud includes at least onecompliant shroud beam radially abutting the case when the needle shroudis in the first extended position and the retracted position, and the atleast one compliant shroud beam deflects radially when the needle shroudis in the second extended position and axially abuts the case.

In an exemplary embodiment, the plunger includes a first plunger bossadapted to engage a shroud rib disposed on the needle shroud and asecond plunger boss adapted to engage a case slot in the case. When theplunger is in the first rotational position and the needle shroud is inthe first extended position, the first plunger boss engages the shroudrib and the second plunger boss engages the case slot. When the needleshroud translates from the first extended position to the retractedposition, the plunger rotates from the first rotational position to thesecond rotational position and the second plunger boss disengages thecase slot. The shroud rib maintains the plunger in the first rotationalposition when the needle shroud is in the first extended position. Theneedle shroud may include a receiving element adapted to receive thefirst plunger boss when the needle shroud is in the retracted positionand the plunger is in the second rotational position.

In an exemplary embodiment, when the needle shroud translates from thefirst extended position to the retracted position, the shroud ribengages a plunger rib to rotate the plunger from the first rotationalposition to the second rotational position. The plunger rib may bedisposed at an angle relative to a longitudinal axis of the case.

Further scope of applicability of the present invention will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating preferred embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will become more fully understood from thedetailed description given hereinbelow and the accompanying drawingswhich are given by way of illustration only, and thus, are not limitiveof the present invention, and wherein:

FIG. 1A is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention during assembly,

FIG. 1B is a schematic side view of an exemplary embodiment of anautoinjector according to the present invention during assembly,

FIG. 2 is a schematic view of an exemplary embodiment of a shroud lockmechanism of an exemplary embodiment of an autoinjector according to thepresent invention,

FIG. 3 is a perspective exploded view of an exemplary embodiment of acontrol subassembly of an exemplary embodiment of an autoinjectoraccording to the present invention,

FIG. 4 is a perspective exploded view of an exemplary embodiment of adrive subassembly of an exemplary embodiment of an autoinjectoraccording to the present invention,

FIG. 5 is a perspective view of an exemplary embodiment of a needlesheath removal mechanism of an exemplary embodiment of an autoinjectoraccording to the present invention,

FIG. 6 is a schematic view of an exemplary embodiment of a plungerrelease mechanism of an exemplary embodiment of an autoinjectoraccording to the present invention,

FIG. 7 is a schematic view of an exemplary embodiment of a plungerrelease mechanism of an exemplary embodiment of an autoinjectoraccording to the present invention during assembly,

FIG. 8 is a schematic view of an exemplary embodiment of a plungerrelease mechanism of an exemplary embodiment of an autoinjectoraccording to the present invention after assembly,

FIG. 9 is a schematic view of an exemplary embodiment of a shroud lockmechanism of an exemplary embodiment of an autoinjector according to thepresent invention after assembly,

FIG. 10 is a schematic view of an exemplary embodiment of shroud lockmechanism of an exemplary embodiment of an autoinjector according to thepresent invention during assembly,

FIG. 11 is a schematic view of an exemplary embodiment of shroud lockmechanism of an exemplary embodiment of an autoinjector according to thepresent invention during assembly,

FIG. 12 is a schematic view of an exemplary embodiment of shroud lockmechanism of an exemplary embodiment of an autoinjector according to thepresent invention during assembly,

FIG. 13 is a schematic view of an exemplary embodiment of shroud lockmechanism of an exemplary embodiment of an autoinjector according to thepresent invention during assembly,

FIG. 14 is a schematic view of an exemplary embodiment of shroud lockmechanism of an exemplary embodiment of an autoinjector according to thepresent invention after assembly,

FIG. 15A is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention after assembly,

FIG. 15B is a schematic side view of an exemplary embodiment of anautoinjector according to the present invention after assembly,

FIG. 16 is a schematic view of an exemplary embodiment of a shroud lockmechanism an exemplary embodiment of an autoinjector according to thepresent invention prior to use,

FIG. 17A is a longitudinal section of an exemplary embodiment of ashroud lock mechanism an exemplary embodiment of an autoinjectoraccording to the present invention prior to use,

FIG. 17B is a schematic side view of an exemplary embodiment of a shroudlock mechanism an exemplary embodiment of an autoinjector according tothe present invention prior to use,

FIG. 18A is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 18B is a schematic side view of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 19 is a schematic view of an exemplary embodiment of a plungerrelease mechanism of an exemplary embodiment of an autoinjectoraccording to the present invention during use,

FIG. 20A is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 20B is a schematic side view of an exemplary embodiment of anautoinjector according to the present invention during use,

FIG. 21A is a longitudinal section of an exemplary embodiment of anautoinjector according to the present invention after use,

FIG. 21B is a schematic side view of an exemplary embodiment of anautoinjector according to the present invention after use,

FIG. 22 is a schematic view of an exemplary embodiment of a shroud lockmechanism of an exemplary embodiment of an autoinjector according to thepresent invention after use, and

FIGS. 23A-E is a schematic view of another exemplary embodiment of aplunger release mechanism during assembly and before, during and afteruse.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

FIG. 1A is a longitudinal section of an exemplary embodiment of anautoinjector 1 according to the present invention during assembly. Theautoinjector 1 comprises a case 2 comprising a front case 2.1 and a rearcase 2.2. The case 2 is adapted to hold a medicament container, such asa syringe 3. The syringe 3 may be a pre-filled syringe and have a needle4 arranged at a distal end. When the autoinjector 1 and/or the syringe 3are assembled, a protective needle sheath 5 may be removably coupled tothe needle 4. The protective needle sheath 5 may be a rubber needlesheath or a rigid needle sheath (which is composed of rubber and a fullor partial plastic shell). A stopper 6 is arranged for sealing thesyringe 3 proximally and for displacing a medicament M contained in thesyringe 3 through the needle 4. In other exemplary embodiments, themedicament container may be a cartridge which includes the medicament Mand engages a removable needle (e.g., by threads, snaps, friction,etc.).

In an exemplary embodiment, a cap 11 may be removably disposed at adistal end of the case 2. The cap 11 may include an element (e.g., abarb, a hook, a narrowed section, etc.) arranged to engage theprotective needle sheath 5, the case 2 and/or a needle shroud 7telescoped within the case 2. The cap 11 may comprise grip features 11.5for facilitating removal of the cap 11 (e.g., by twisting and/or pullingthe cap 11.5 relative to the case 2).

In an exemplary embodiment, a shroud spring 8 is arranged to bias theneedle shroud 7 in a distal direction D against the case 2.

In an exemplary embodiment, a drive spring 9 is arranged within the case2. A plunger 10 serves for forwarding a force of the drive spring 9 tothe stopper 6. In an exemplary embodiment, the plunger 10 is hollow andthe drive spring 9 is arranged within the plunger 10 biasing the plunger10 in the distal direction D against the case 2. In another exemplaryembodiment, the plunger 10 may be solid and the drive spring 9 mayengage a proximal end of the plunger 10.

In an exemplary embodiment, a plunger release mechanism 12 is arrangedfor preventing release of the plunger 10 prior to retraction of theneedle shroud 7 relative to the case 2 and for releasing the plunger 10once the needle shroud 7 is sufficiently retracted.

In an exemplary embodiment, a first shroud lock mechanism 14 is arrangedto prevent retraction of the needle shroud 7 relative to the case 2 whenthe cap 11 is in place, thereby avoiding unintentional activation of theautoinjector 1 (e.g., if dropped, during shipping or packaging, etc.).The first shroud lock mechanism 14 may comprise one or more compliantbeams 11.3 on the cap 11 and a respective number of apertures 7.6 in theneedle shroud 7 adapted to receive each of the compliant beams 11.3.When the cap 11 is attached to the autoinjector 1, the compliant beams11.3 abut a radial stop 2.15 on the case 2 which prevents the compliantbeams 11.3 from disengaging the apertures 7.6. When the cap 11 isattached to the autoinjector 1, axial movement of the cap 11 in theproximal direction P relative the case 2 is limited by a rib 11.4 on thecap 11 abutting the case 2. When the cap 11 is pulled in the distaldirection D relative to the case 2, the compliant beams 11.3 may abut anedge of the aperture 7.6 and deflect to disengage the aperture 7.6,allowing for removal of the cap 11 and the protective needle sheath 5attached thereto. In an exemplary embodiment, the compliant beams 11.3and/or the apertures 7.6 may be ramped to reduce force necessary todisengage the compliant beams 11.3 from the apertures 7.6.

FIG. 1B is a schematic side view of an exemplary embodiment of theautoinjector 1 according to the prevent invention during assembly. Inthe exemplary embodiment in FIG. 1B, the case 2 is removed for clarity.FIG. 1B and FIG. 2 show a second shroud lock mechanism 15 that isadapted to lock the needle shroud 7 in an axial position relative to thecase 2 after the autoinjector 1 has been removed from the injectionsite. In an exemplary embodiment, the second shroud lock mechanism 15comprises at least one compliant shroud beam 7.1 on the needle shroud 7adapted to proximally abut a stop 2.12 on the case 2 after theautoinjector 1 has been removed from the injection site. The abutment ofthe shroud beam 7.1 on the stop 2.12 prevents translation of the needleshroud 7 in the proximal direction P relative to the case 2. Prior touse, when the cap 11 is attached to the autoinjector 1, the cap 11 isadapted to engage and deflect the compliant shroud beam 7.1 radiallyinward, allowing the shroud beam 7.1 to pass the stop 2.12 in theproximal direction P so that the needle shroud 7 can translate in theproximal direction P relative to the case 2.

In an exemplary embodiment, the autoinjector 1 may formed from at leasttwo subassemblies, e.g., a control subassembly 1.1 and a drivesubassembly 1.2, to allow for flexibility as to the time and location ofmanufacture of the subassemblies 1.1, 1.2 and final assembly with thesyringe 3.

FIG. 3 is a perspective exploded view of an exemplary embodiment of acontrol subassembly 1.1 of an autoinjector 1 according to the presentinvention. In an exemplary embodiment, the control subassembly 1.1comprises the cap 11, the needle shroud 7, the shroud spring 8 and thefront case 2.1. To assemble the control subassembly 1.1, the shroudspring 8 is inserted into the needle shroud 7, and the needle shroud 7with the shroud spring 8 is inserted into the front case 2.1. The cap 11is arranged over the distal end of the needle shroud 7.

FIG. 4 is a perspective exploded view of an exemplary embodiment of adrive subassembly 1.2 of an autoinjector 1 according to the presentinvention. In an exemplary embodiment, the drive subassembly 1.2 theplunger 10, the drive spring 9 and the rear case 2.2. Those of skill inthe art will understand that if the viscosity or volume, for example, ofthe medicament M in the syringe 3 is changed, only parts of the drivesubassembly 1.2 may need to be changed. To assemble the drivesubassembly 1.2, the drive spring 9 is inserted into the plunger 10 andthe plunger 10 is inserted in the rear case 2.2 in the proximaldirection P thereby compressing the drive spring 9. Once the plunger 10and the drive spring 9 reach a compressed position it is rotated by anangle, e.g. approximately 30° relative to the rear case 2.2, to engagethe plunger 10 to the rear case 2.2. In an exemplary embodiment, therear case 2.2 may have a cam surface to engage the plunger 10 to inducethis rotation prior to the plunger 10 and the drive spring 9 reachingthe compressed position.

FIG. 5 is a perspective view of an exemplary embodiment of a needlesheath removal mechanism 13 of an autoinjector 1 according to thepresent invention. The needle sheath removal mechanism 13 comprises anopening 11.1 axially arranged in the cap 11. The opening 11.1 isapproximately sized and shaped to receive the protective needle sheath5. One or more bosses 11.2 may be disposed on a proximal end of the cap11 and adapted to abut the protective needle sheath 5. For example, whenthe protective needle sheath 5 is inserted into the opening 11.1, theprotective needle sheath 5 may deform around the bosses 11.2. The bosses11.2 may be ramped to reduce force necessary to insert the protectiveneedle sheath 5 into the opening 11.1. Once the protective needle sheath5 has passed the bosses 11.2 in the distal direction D, the bosses 11.2may abut a proximal end of the protective needle sheath 5 to preventtranslation of the protective needle sheath 5 in the proximal directionP relative to the cap 11. For example, during removal of the cap 11 fromthe autoinjector 1, the bosses 11.2 on the cap 11 may abut the proximalend of the protective needle sheath 5 and push the protective needlesheath 5 in the distal direction D off of the needle 4. with theirnon-ramped distal face. Those of skill in the art will understand that anumber of parameters can be varied, e.g. a radial height of the boss11.2, an axial length of the boss 11.2, an angle of the ramp of the boss11.2, a durometer of the protective needle sheath 5, a surface finish ofthe boss 11.2, etc., which could increase or decrease assembly forces,cap removal forces, etc.

FIG. 6 is a schematic view of an exemplary embodiment of a plungerrelease mechanism 12 of the autoinjector 1 according to the presentinvention during assembly. The plunger release mechanism 12 is arrangedfor preventing release of the plunger 10 prior to retraction of theneedle shroud 7 relative to the case 2 and for releasing the plunger 10once the needle shroud 7 is sufficiently retracted. In an exemplaryembodiment, the plunger release mechanism 12 comprises the plunger 10,the rear case 2.2, and the needle shroud 7 interacting with each other.In an exemplary embodiment, the needle shroud 7 is limited to axialmovement relative to the case 2, and the plunger 10 can translateaxially and rotate relative to the case 2.

In an exemplary embodiment, the plunger 10 comprises a first plungerboss 10.1 adapted to engage a shroud rib 7.7 on the needle shroud 7, asecond plunger boss 10.2 adapted to engage a case slot 2.3 in the case2, and a plunger rib 10.3 adapted to engage the shroud rib 7.7 on theneedle shroud 7. In an exemplary embodiment, the shroud rib 7.7comprises a proximal face 7.8 adapted to engage the plunger rib 10.3,and a distal face 7.9 and a longitudinal face 7.10 adapted to engage thefirst plunger boss 10.1. A receiving element (e.g., a recess, a hole,etc.) may be formed on the needle shroud 7 distal of the longitudinalface 7.10 of the shroud rib 7.7. In an exemplary embodiment, the caseslot 2.3 comprises a first angled surface 2.9 adapted to apply arotational force in a first rotational direction R1 to the secondplunger boss 10.2, a wall 2.10 adapted to abut the second plunger boss10.2 to limit rotation of the plunger 10 relative to the case 2 in thefirst rotational direction R1, and a second angled surface 2.11 adaptedto apply a rotational force in a second rotational direction R2,opposite the first rotational direction R1, to the second plunger boss10.2.

In an exemplary embodiment of an assembly process of the drivesubassembly 1.2, the plunger 10 with the drive spring 9 is inserted intothe rear case 2.2. When the second plunger boss 10.2 is axially alignedwith the case slot 2.3, the plunger 10 is rotated in the firstrotational direction R1 until the second plunger boss 10.2 is moved intothe case slot 2.3 until it abuts the wall 2.10. In this position, thefirst angled surface 2.9 prevents the second plunger boss 10.2 frommoving in the second rotational direction R2, and thus prevents theplunger 10 from rotating relative to the case 2.

After a syringe 3 (with the protective needle sheath 5 disposed on theneedle 4) is inserted into the control assembly 1.1, the drivesubassembly 1.2 is coupled to the control subassembly 1.1. In anexemplary embodiment, a pair of resilient beams 2.13 (shown in FIG. 1B)on the rear case 2.2 is adapted to snap into recesses 2.14 (shown inFIG. 3 ) in the front case 2.1 to lock the drive subassembly 1.2 to thecontrol subassembly 1.1. As the drive assembly 1.2 is coupled to thecontrol subassembly 1.1, the needle shroud 7 translates proximally(e.g., by use of an assembly jig) causing the shroud rib 7.7 to abut theplunger rib 10.3. As shown in FIG. 7 , as the shroud rib 7.7 pushesplunger rib 10.3, the angle of the plunger rib 10.3 causes the plunger10 to rotate relative to the case 2 in the second rotational directionR2, and the second plunger boss 10.2 rides along the first angledsurface 2.9 onto the second angled surface 2.11. When the second plungerboss 10.2 is disposed on the second angled surface 2.11, the force ofthe drive spring 9 imparts a rotational force on the plunger 10 in thesecond rotational direction R2 due to the angle of the second angledsurface 2.11.

As shown in FIG. 8 , when the needle shroud 7 is released (e.g., byremoving the assembly jig), the needle shroud 7 translates in the distaldirection D relative to the case 2 under the force the shroud spring 8until the shroud rib 7.7 abuts the first plunger boss 10.1. For example,the distal face 7.9 of the shroud rib 7.7 may abut the first plungerboss 10.1 and maintain the needle shroud 7 in an axial position relativeto the case 2. The second plunger boss 10.2 is prevented fromdisengaging the case slot 2.3, because the shroud rib 7.7 prevents theplunger 10 from rotating in the second rotational direction R2 relativeto the case 2. For example, the longitudinal face 7.10 of the shroud rib7.7 abuts the first plunger boss 10.1 to prevent rotation of the plunger10.

FIG. 9 shows an exemplary embodiment of the first shroud lock mechanism14 for an autoinjector 1 according to the present invention afterassembly of the control subassembly 1.1. The compliant beam 11.3 on thecap is engaged in the aperture 7.6 within the needle shroud 7. Theradial stop 2.15 is axially spaced from the compliant beam 11.3.

FIG. 10 shows an exemplary embodiment of the first shroud lock mechanism14 for an autoinjector 1 according to the present invention duringinsertion of the syringe 3 into the control subassembly 1.1 for engagingthe protective needle sheath 5 to the cap 11. The aperture 7.6 providessome clearance allowing a movement of the needle shroud 7 relative tothe cap 11 in the distal direction D. The front case 2.1 is also movedin the distal direction D relative to the cap 11 axially aligning theradial stop 2.15 with the compliant beam 11.3 preventing the cap 11 fromdisengaging the needle shroud 7.

FIG. 11 shows an exemplary embodiment of the first shroud lock mechanism14 for an autoinjector 1 according to the present invention, whereinafter insertion of the syringe 3, the needle shroud 7 is moved furtherin the proximal direction P relative to the front case 2.1 by anassembly jig (not illustrated). In this state, the drive subassembly 1.2may be assembled to the control subassembly 1.1. The compliant beam 11.3remains engaged in the aperture 7.6 and the radial stop 2.15 preventsthem from disengaging.

After assembly of the drive subassembly 1.2 to the control subassembly1.1, the assembly jig is removed allowing the needle shroud 7 to moveback in the distal direction D relative to the front case 2.1 under theforce of the shroud spring 8 arriving again in the state illustrated inFIG. 10 . In this configuration, the needle shroud 7 is prevented frommoving in the proximal direction P relative to the case 2, because theradial stop 2.15 prevents the compliant beam 11.3 from disengaging theaperture 7.6 and the rib 11.4 on the cap 11 proximally abuts the frontcase 2.1.

FIG. 12 shows an exemplary embodiment of the second shroud lockmechanism 15 for an autoinjector 1 according to the present inventionafter assembly of the control subassembly 1.1. The needle shroud 7 ispartially inserted into the cap 11. The shroud beam 7.1 is in anon-deflected position proximally abutting the stop 2.12 in the frontcase 2.1. This prevents the needle shroud 7 from moving further in theproximal direction P relative to the front case 2.1 and keeps thecontrol subassembly 1.1 locked together.

FIG. 13 shows an exemplary embodiment of the second shroud lockmechanism 15 for an autoinjector 1 according to the present inventionduring insertion of the syringe 3 into the control subassembly 1.1,wherein the needle shroud 7 is moved further in the distal direction Dinto the cap 11 such that the cap 11 radially inwardly deflects theshroud beam 7.1 out of its abutment with the stop 2.12. The needleshroud 7 is thus free to move in the proximal direction P relative tothe front case 2.1.

FIG. 14 shows an exemplary embodiment of the second shroud lockmechanism 15 for an autoinjector 1 according to the present inventionafter final assembly of the drive subassembly 1.2 to the controlsubassembly 1.1. The needle shroud 7 has been moved further in theproximal direction P relative the front case 2.1 by an assembly jig (notillustrated). In this state, the drive subassembly 1.2 may be assembledto the control subassembly 1.1. Subsequently, the assembly jig isremoved and the needle shroud 7 translates in the distal direction Drelative to the front case 2.1 under the force of the shroud spring 8until the shroud rib 7.7 abuts the first plunger boss 10.1. The shroudbeam 7.1 is prevented from deflecting radially outward by the stop 2.12in the front case 2.1.

FIG. 15A is a longitudinal section of an exemplary embodiment of anautoinjector 1 according to the present invention after final assembly,and FIG. 15B is a schematic side view of an exemplary embodiment of anautoinjector 1 according to the present invention after final assembly,wherein the case 2 is removed for clarity.

In an exemplary embodiment, after the final assembly of the drivesubassembly 1.2 to the control subassembly 1.1, the autoinjector 1 maybe kept in temperature controlled environment (e.g., cold chain storage)to, for example, reduce creep in highly stressed components, e.g. underload from the drive spring 9.

An exemplary sequence of operation of an exemplary embodiment of theautoinjector 1 is as follows:

If applicable, the autoinjector 1 is removed from the packaging. Themedicament in the syringe 3 may be visually inspected through a viewingwindow (not shown), which can be a transparent part of the case 2 or acut-out in the case 2 aligned with the syringe 3.

The cap 11 is removed by pulling it in the distal direction D away fromthe case 2. As the cap 11 translates distally relative to the case 2,the bosses 11.2 on the cap 11 frictionally engage the protective needlesheath 5 and pull it off the needle 4 as the cap 11 is pulled in thedistal direction D, and the compliant beam 11.3 disengages the aperture7.6 in the needle shroud 7, as shown in FIG. 16 . The compliant beam11.3 translates distally within the aperture 7.6 until it is no longerabutted radially by the radial stop 2.15 and engages a proximal surfaceof the aperture 7.6 (which may be ramped) and deflects radially todisengage the aperture 7.6. The syringe 3 is fixed in position relativeto the case 2, so pulling the cap 11 in the distal direction D does notcause any axial movement of the syringe 3. In an exemplary embodiment,the syringe 3 is also fixedly rotationally relative to the case 2 (e.g.,by an interference fit with the case 2 and/or the needle shroud 7).

FIG. 17A is a longitudinal section of an exemplary embodiment of theautoinjector 1 according to the present invention prior to use. FIG. 17Bis a schematic side view of an exemplary embodiment of the autoinjector1 according to the present invention prior to use, wherein the case 2 isremoved for clarity.

When the cap 11 is removed, the needle shroud 7 is in a first extendedposition FEP relative to the case 2, protruding from the case 2 in thedistal direction D. The first extended position FEP is defined by thefirst plunger boss 10.1 abutting the shroud rib 7.7.

FIG. 18A is a longitudinal section of an exemplary embodiment of theautoinjector 1 according to the present invention during use. FIG. 18Bis a schematic side view of an exemplary embodiment of the autoinjector1 according to the present invention during use, wherein the case 2 isremoved for clarity.

When the autoinjector 1 is pressed against an injection site, the needleshroud 7 translates proximally relative to the case 2 against thebiasing force of the shroud spring 8 from the first extended positionFEP to a retracted position RP, as shown in FIGS. 18A and 18B.

FIG. 19 shows an exemplary embodiment of the plunger release mechanism12 when the needle shroud 7 is in the retracted position RP. As theneedle shroud 7 translates from the first extended position FEP to theretracted position RP, the needle shroud 7 translates distally causingthe first plunger boss 10.1 to, starting from the position shown in FIG.8 , ride along the shroud rib 7.7 until it is distal of the shroud rib7.7. When the first plunger boss 10.1 is distal of the shroud rib 7.7and may be accommodated by the receiving element, the plunger 10 is nolonger prevented from rotating in the second rotational direction R2relative to the case 2. Thus, the force of the drive spring 9 on theplunger 10 and the engagement of the second plunger boss 10.2 on thesecond angled surface 2.11 in the case slot 2.3, causes the plunger 10to rotate relative to the case 2. In an exemplary embodiment, the needleshroud 7 may include an aperture, a recess or a slot proximal of theshroud rib 7.7 to accommodate the first plunger boss 10.1 when theneedle shroud 7 is in the retracted position RP and the plunger 10rotates relative to the case 2.

In an exemplary embodiment, the shroud rib 7.7 (e.g., on thelongitudinal face 7.10) may include a resistance feature (e.g., aprojection, a ramp, a recess, etc.) adapted to abut the first plungerboss 10.1 as the needle shroud 7 translates from the first extendedposition FEP to the retracted position RP. When the first plunger boss10.1 abuts the resistance feature, a tactile feedback is provided in theform of increased resistance to pressing the autoinjector 1 against theinjection site. The tactile feedback may be used to indicate that needle4 will be inserted into the injection site upon further depression ofthe autoinjector 1 against the injection site. Prior to the needleshroud 7 reaching the retracted position RP, if the autoinjector 1 isremoved from the injection site, the needle shroud and reposition as theneedle shroud 7 will re-extend to its initial position under the forceof the shroud spring 8. When the needle shroud 7 is in the retractedposition RP, the needle 4 has been inserted into the injection site.Those of skill in the art will understand that a penetration depth ofthe needle 4 may be varied by, for example, limiting retraction of theneedle shroud 7 relative to the case 2, modifying an axial position ofthe syringe 3 relative to the case 2, modifying a length of the needle4, etc. Thus, the autoinjector 1 of the present invention may be usedfor sub-cutaneous, intra-dermal and/or intra-muscular injection.

FIG. 20A is a longitudinal section of an exemplary embodiment of theautoinjector 1 according to the present invention during use. FIG. 20Bis a schematic side view of an exemplary embodiment of the autoinjector1 according to the present invention during use, wherein the case 2 isremoved for clarity.

When the plunger 10 has rotated a sufficient distance in the secondrotational direction R2 such that the second plunger boss 10.2disengages the case slot 2.3, the plunger 10 is free to translateaxially, under the force of the drive spring 9, relative to the case 2to push the stopper 6 to deliver the medicament M from the syringe 3through the needle 4.

In an exemplary embodiment, disengagement of the first plunger boss 10.1from the shroud rib 7.7 and/or the second plunger boss 10.2 from thecase slot 2.3 may provide an audible feedback indicating that deliveryof the medicament M has started. A viewing window in the case 2 mayallow for a visual feedback that the plunger 10 is advancing within thesyringe 3 for assessing the progress of displacement of the medicamentM.

FIG. 21A is a longitudinal section of an exemplary embodiment of theautoinjector 1 according to the present invention after use. FIG. 21B isa schematic side view of an exemplary embodiment of the autoinjector 1according to the present invention after use, wherein the case 2 isremoved for clarity.

When the autoinjector 1 is removed from the injection site, the needleshroud 7 translates distally relative to the case 2 from the retractedposition RP to a second extended position SEP under the biasing force ofthe shroud spring 8. In the second extended position SEP, the needleshroud 7 extends beyond a distal tip of the needle 4 and locks in anaxial position relative to the case 2. The second extended position SEPprevents needle-stick injury and may also indicate that the autoinjector1 has been used (because the needle shroud 7 cannot move proximally fromthe second extended position SEP). In an exemplary embodiment, in thesecond extended position SEP, the needle shroud 7 protrudes further,e.g. 2 mm, from the case 2 than in the first extended position FEP. Theneedle shroud 7 may include an indicia (e.g., a red ring, text, agraphic) on a portion which is visually accessible when the needleshroud 7 is in the second extended position SEP but not in the firstextended position FEP. The indicia may indicate that the autoinjector 1has been used.

FIG. 22 is a schematic view of an exemplary embodiment of the secondshroud lock mechanism 15 according to the present invention. As theneedle shroud 7 translates from the retracted position RP toward thesecond extended position SEP, the shroud beam 7.1 passes the stop 2.12in the distal direction D and relaxes radially outwards which ispossible as the cap 11 is no longer present. In the second extendedposition SEP, the needle shroud 7 cannot translate proximally relativeto the case 2, because the shroud beam 7.1 abuts the stop 2.12. Theneedle shroud 7 is thus locked in the second extended position SEP.Extension of the needle shroud 7 distally beyond the second extendedposition SEP may be prevented by a shroud boss 7.2 on the needle shroud7 that abuts a case boss 2.8 on the case 2 (see FIG. 1 ).

FIGS. 23A to 23E are schematic views of another exemplary embodiment ofa plunger release mechanism 12 of the autoinjector 1 according to thepresent invention. The plunger release mechanism 12 is arranged forpreventing release of the plunger 10 prior to retraction of the needleshroud 7 relative to the case 2 and for releasing the plunger 10 oncethe needle shroud 7 is sufficiently retracted. In an exemplaryembodiment, the plunger release mechanism 12 comprises the plunger 10,the rear case 2.2, and the needle shroud 7. In this exemplaryembodiment, the needle shroud 7 is limited to axial movement relative tothe case 2, and the plunger 10 can translate axially and rotate relativeto the case 2.

In the exemplary embodiment shown in FIGS. 23A-E, the plunger 10comprises a first plunger boss 10.1 adapted to engage a shroud rib 7.7on the needle shroud 7, a second plunger boss 10.2 adapted to engage acase slot 2.3 in the case 2, and a plunger rib 10.3 adapted to engagethe shroud rib 7.7 on the needle shroud 7. In an exemplary embodiment,the shroud rib 7.7 is disposed in a plane substantially perpendicular toa longitudinal axis of the case 2. The shroud 7.7 comprises a proximalface 7.8 adapted to engage the plunger rib 10.3, and a distal face 7.9adapted to engage the first plunger boss 10.1. In an exemplaryembodiment, the case slot 2.3 comprises a first angled surface 2.9adapted to apply a rotational force in a first rotational direction R1to the second plunger boss 10.2, a wall 2.10 adapted to abut the secondplunger boss 10.2 to limit rotation of the plunger 10 relative to thecase 2 in the first rotational direction R1, and a transversal surface2.16 disposed in a plane substantially perpendicular to a longitudinalaxis of the case 2.

FIG. 23A is a schematic view of an exemplary embodiment of the plungerrelease mechanism 12 of the autoinjector 1 according to the presentinvention during assembly of the drive subassembly 1.2. During assemblyof the drive subassembly 1.2, the plunger 10 with the drive spring 9 isinserted into the rear case 2.2. When the second plunger boss 10.2 isaxially aligned with the case slot 2.3, the plunger 10 is rotated in thefirst rotational direction R1 until the second plunger boss 10.2 ismoved into the case slot 2.3 until it abuts the wall 2.10. In thisposition, the first angled surface 2.9 prevents the second plunger boss10.2 from moving in the second rotational direction R2, and thusprevents the plunger 10 from rotating relative to the case 2.

After a syringe 3 (with the protective needle sheath 5 disposed on theneedle 4) is inserted into the control assembly 1.1, the drivesubassembly 1.2 is coupled to the control subassembly 1.1. In anexemplary embodiment, a pair of resilient beams 2.13 (shown in FIG. 1B)on the rear case 2.2 is adapted to snap into recesses 2.14 (shown inFIG. 3 ) in the front case 2.1 to lock the drive subassembly 1.2 to thecontrol subassembly 1.1. FIG. 23B shows the drive assembly 1.2 beingcoupled to the control subassembly 1.1, wherein the needle shroud 7translates proximally (e.g., by use of an assembly jig) causing theshroud rib 7.7 to abut the plunger rib 10.3. As shown in FIG. 23C, asthe needle shroud rib 7.7 pushes the plunger rib 10.3, the angle of theplunger rib 10.3 causes the plunger 10 to rotate relative to the case 2in the second rotational direction R2, and the second plunger boss 10.2rides along the first angled surface 2.9 onto the transversal surface2.16.

As shown in FIG. 23D, when the needle shroud 7 is released (e.g., byremoving the assembly jig), the needle shroud 7 translates in the distaldirection D relative to the case 2 under the force of the shroud spring8 until the shroud rib 7.7 abuts the first plunger boss 10.1. Forexample, the distal face 7.9 of the shroud rib 7.7 may abut the firstplunger boss 10.1 and maintain the needle shroud 7 in an axial positionrelative to the case 2. The second plunger boss 10.2 is prevented fromdisengaging the case slot 2.3 as it abuts the transversal surface 2.16in the distal direction D.

FIG. 23E shows an exemplary embodiment of the plunger release mechanism12 when the needle shroud 7 is in the retracted position RP. As theneedle shroud 7 translates from the first extended position FEP to theretracted position RP, the needle shroud 7 translates distally causingthe shroud rib 7.7 to, starting from the position shown in FIG. 23D,ride along the plunger rib 10.3 thereby rotating the second plunger boss10.2 in the second rotational direction R2 along the transversal surface2.16 until the second plunger boss 10.2 disengages the case slot 2.3thus releasing the plunger 10. Then, under the force of the drive spring9, the plunger 10 translates axially relative to the case 2 to deliverthe medicament M from the syringe 3. In this exemplary embodiment, atactile feedback may be provided in the form of an increase inresistance when the needle shroud 7 abuts and pushes against the plungerrib 10.3. The tactile feedback may indicate that needle insertion willcommence or medicament delivery will be initiated if the autoinjector 1is pressed further against the injection site.

In an exemplary embodiment the transversal surface 2.16 could bereplaced by or comprise a concave shape for preventing inadvertentrelease of the plunger 10.

In another exemplary embodiment, the plunger 10 may not have the firstplunger boss 10.1, the plunger rib 10.3 may be disposed at differentangle than as described above, and the case slot 2.3 may not be angledrelative to a transverse axis of the case 2. In this exemplaryembodiment, when the autoinjector 1 is assembled, the plunger 10 ismaintained in axial position relative to the case 2, because the secondplunger boss 10.2 engages the case slot 2.3. However, the case slot 2.3may not impart any rotational force on the second plunger boss 10.2 (or,in another exemplary embodiment, the case slot 2.3 may be angled toimpart a rotational force on the second plunger boss 10.2 in the firstrotational direction R1 to ensure that the second plunger boss 10.2 doesnot disengage the case slot 2.3 inadvertently).

In an exemplary embodiment, a tamper strip (not shown) may be arrangedbetween the cap 11 and the front case 2.1 when the control subassembly1.1 is assembled. The tamper strip may be useful for quality assurance.

In an exemplary embodiment, a force required to press the needle shroud7 may be approximately 2-12 N.

In an exemplary embodiment, the syringe 3 used in the autoinjector 1 maybe a syringe capable of containing approximately 1 mL of the medicamentM. In another exemplary embodiment, the syringe 3 used in theautoinjector 1 may be a syringe capable of containing approximately 2 mLof the medicament M.

The autoinjector 1 according to the present invention may have anincreased shelf-life compared to conventional autoinjectors, because,for example, only the plunger 10 is subjected to the relatively highforce of the drive spring 9.

The autoinjector 1 according to the present invention may be used as aplatform as the drive spring 9 can be changed to alter a force appliedto the plunger 10, e.g., for delivering medicaments with differentviscosities drugs or reconstituted medicaments, or changing a timerequired to inject a dose of the medicament.

The term “drug” or “medicament”, as used herein, means a pharmaceuticalformulation containing at least one pharmaceutically active compound,

wherein in one embodiment the pharmaceutically active compound has amolecular weight up to 1500 Da and/or is a peptide, a proteine, apolysaccharide, a vaccine, a DNA, a RNA, an enzyme, an antibody or afragment thereof, a hormone or an oligonucleotide, or a mixture of theabove-mentioned pharmaceutically active compound,

wherein in a further embodiment the pharmaceutically active compound isuseful for the treatment and/or prophylaxis of diabetes mellitus orcomplications associated with diabetes mellitus such as diabeticretinopathy, thromboembolism disorders such as deep vein or pulmonarythromboembolism, acute coronary syndrome (ACS), angina, myocardialinfarction, cancer, macular degeneration, inflammation, hay fever,atherosclerosis and/or rheumatoid arthritis,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one peptide for the treatment and/or prophylaxis ofdiabetes mellitus or complications associated with diabetes mellitussuch as diabetic retinopathy,

wherein in a further embodiment the pharmaceutically active compoundcomprises at least one human insulin or a human insulin analogue orderivative, glucagon-like peptide (GLP-1) or an analogue or derivativethereof, or exendin-3 or exendin-4 or an analogue or derivative ofexendin-3 or exendin-4.

Insulin analogues are for example Gly(A21), Arg(B31), Arg(B32) humaninsulin; Lys(B3), Glu(B29) human insulin; Lys(B28), Pro(B29) humaninsulin; Asp(B28) human insulin; human insulin, wherein proline inposition B28 is replaced by Asp, Lys, Leu, Val or Ala and wherein inposition B29 Lys may be replaced by Pro; Ala(B26) human insulin;Des(B28-B30) human insulin; Des(B27) human insulin and Des(B30) humaninsulin.

Insulin derivates are for example B29-N-myristoyl-des(B30) humaninsulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoyl humaninsulin; B29-N-palmitoyl human insulin; B28-N-myristoyl LysB28ProB29human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30human insulin; B29-N-(N-palmitoyl-Y-glutamyl)-des(B30) human insulin;B29-N-(N-lithocholyl-Y-glutamyl)-des(B30) human insulin;B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(w-carboxyheptadecanoyl) human insulin.

Exendin-4 for example means Exendin-4(1-39), a peptide of the sequenceH-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-Arg-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2.

Exendin-4 derivatives are for example selected from the following listof compounds:

H-(Lys)4-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

H-(Lys)5-des Pro36, des Pro37 Exendin-4(1-39)-NH2,

des Pro36 Exendin-4(1-39),

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28]Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39); or

des Pro36 [Asp28] Exendin-4(1-39),

des Pro36 [IsoAsp28]Exendin-4(1-39),

des Pro36 [Met(O)14, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14, IsoAsp28]Exendin-4(1-39),

des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Trp(O2)25, IsoAsp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, Asp28] Exendin-4(1-39),

des Pro36 [Met(O)14 Trp(O2)25, IsoAsp28] Exendin-4(1-39),

wherein the group -Lys6-NH2 may be bound to the C-terminus of theExendin-4 derivative;

or an Exendin-4 derivative of the sequence

des Pro36 Exendin-4(1-39)-Lys6-NH2 (AVE0010),

H-(Lys)6-des Pro36 [Asp28] Exendin-4(1-39)-Lys6-NH2,

des Asp28 Pro36, Pro37, Pro38Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro38 [Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Trp(O2)25] Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36 [Met(O)14, Asp28] Exendin-4(1-39)-Lys6-NH2,

des Met(O)14 Asp28 Pro36, Pro37, Pro38 Exendin-4(1-39)-NH2,

H-(Lys)6-desPro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Asn-(Glu)5 des Pro36, Pro37, Pro38 [Met(O)14, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-Lys6-des Pro36 [Met(O)14, Trp(O2)25, Asp28] Exendin-4(1-39)-Lys6-NH2,

H-des Asp28 Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25]Exendin-4(1-39)-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Asp28] Exendin-4(1-39)-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-NH2,

des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2,

H-(Lys)6-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(S1-39)-(Lys)6-NH2,

H-Asn-(Glu)5-des Pro36, Pro37, Pro38 [Met(O)14, Trp(O2)25, Asp28]Exendin-4(1-39)-(Lys)6-NH2;

or a pharmaceutically acceptable salt or solvate of any one of theafore-mentioned Exendin-4 derivative.

Hormones are for example hypophysis hormones or hypothalamus hormones orregulatory active peptides and their antagonists as listed in RoteListe, ed. 2008, Chapter 50, such as Gonadotropine (Follitropin,Lutropin, Choriongonadotropin, Menotropin), Somatropine (Somatropin),Desmopressin, Terlipressin, Gonadorelin, Triptorelin, Leuprorelin,Buserelin, Nafarelin, Goserelin.

A polysaccharide is for example a glucosaminoglycane, a hyaluronic acid,a heparin, a low molecular weight heparin or an ultra low molecularweight heparin or a derivative thereof, or a sulphated, e.g. apoly-sulphated form of the above-mentioned polysaccharides, and/or apharmaceutically acceptable salt thereof An example of apharmaceutically acceptable salt of a poly-sulphated low molecularweight heparin is enoxaparin sodium.

Antibodies are globular plasma proteins (˜150 kDa) that are also knownas immunoglobulins which share a basic structure. As they have sugarchains added to amino acid residues, they are glycoproteins. The basicfunctional unit of each antibody is an immunoglobulin (Ig) monomer(containing only one Ig unit); secreted antibodies can also be dimericwith two Ig units as with IgA, tetrameric with four Ig units liketeleost fish IgM, or pentameric with five Ig units, like mammalian IgM.

The Ig monomer is a “Y”-shaped molecule that consists of fourpolypeptide chains; two identical heavy chains and two identical lightchains connected by disulfide bonds between cysteine residues. Eachheavy chain is about 440 amino acids long; each light chain is about 220amino acids long. Heavy and light chains each contain intrachaindisulfide bonds which stabilize their folding. Each chain is composed ofstructural domains called Ig domains. These domains contain about 70-110amino acids and are classified into different categories (for example,variable or V, and constant or C) according to their size and function.They have a characteristic immunoglobulin fold in which two β sheetscreate a “sandwich” shape, held together by interactions betweenconserved cysteines and other charged amino acids.

There are five types of mammalian Ig heavy chain denoted by α, β, ε, γ,and μ. The type of heavy chain present defines the isotype of antibody;these chains are found in IgA, IgD, IgE, IgG, and IgM antibodies,respectively.

Distinct heavy chains differ in size and composition; α and γ containapproximately 450 amino acids and δ approximately 500 amino acids, whileμ and ε have approximately 550 amino acids. Each heavy chain has tworegions, the constant region (C_(H)) and the variable region (V_(H)). Inone species, the constant region is essentially identical in allantibodies of the same isotype, but differs in antibodies of differentisotypes. Heavy chains γ, α and δ have a constant region composed ofthree tandem Ig domains, and a hinge region for added flexibility; heavychains μ and ε have a constant region composed of four immunoglobulindomains. The variable region of the heavy chain differs in antibodiesproduced by different B cells, but is the same for all antibodiesproduced by a single B cell or B cell clone. The variable region of eachheavy chain is approximately 110 amino acids long and is composed of asingle Ig domain.

In mammals, there are two types of immunoglobulin light chain denoted byλ and κ. A light chain has two successive domains: one constant domain(CL) and one variable domain (VL). The approximate length of a lightchain is 211 to 217 amino acids. Each antibody contains two light chainsthat are always identical; only one type of light chain, κ or λ, ispresent per antibody in mammals.

Although the general structure of all antibodies is very similar, theunique property of a given antibody is determined by the variable (V)regions, as detailed above. More specifically, variable loops, threeeach the light (VL) and three on the heavy (VH) chain, are responsiblefor binding to the antigen, i.e. for its antigen specificity. Theseloops are referred to as the Complementarity Determining Regions (CDRs).Because CDRs from both VH and VL domains contribute to theantigen-binding site, it is the combination of the heavy and the lightchains, and not either alone, that determines the final antigenspecificity.

An “antibody fragment” contains at least one antigen binding fragment asdefined above, and exhibits essentially the same function andspecificity as the complete antibody of which the fragment is derivedfrom. Limited proteolytic digestion with papain cleaves the Ig prototypeinto three fragments. Two identical amino terminal fragments, eachcontaining one entire L chain and about half an H chain, are the antigenbinding fragments (Fab). The third fragment, similar in size butcontaining the carboxyl terminal half of both heavy chains with theirinterchain disulfide bond, is the crystalizable fragment (Fc). The Fccontains carbohydrates, complement-binding, and FcR-binding sites.Limited pepsin digestion yields a single F(ab′)2 fragment containingboth Fab pieces and the hinge region, including the H-H interchaindisulfide bond. F(ab′)2 is divalent for antigen binding. The disulfidebond of F(ab′)2 may be cleaved in order to obtain Fab′. Moreover, thevariable regions of the heavy and light chains can be fused together toform a single chain variable fragment (scFv).

Pharmaceutically acceptable salts are for example acid addition saltsand basic salts. Acid addition salts are e.g. HCl or HBr salts. Basicsalts are e.g. salts having a cation selected from alkali or alkaline,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are described in “Remington'sPharmaceutical Sciences” 17. ed. Alfonso R. Gennaro (Ed.), MarkPublishing Company, Easton, Pa., U.S.A., 1985 and in Encyclopedia ofPharmaceutical Technology.

Pharmaceutically acceptable solvates are for example hydrates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the apparatuses, methodsand/or systems and embodiments described herein may be made withoutdeparting from the full scope and spirit of the present invention, whichencompass such modifications and any and all equivalents thereof.

1. An autoinjector (1) comprising: a case (2) adapted to hold a medicament container having a needle (4); a needle shroud (7) telescopically coupled to the case (2) and movable between a first extended position (FEP) relative to the case (2) in which the needle (4) is covered and a retracted position (RP) relative to the case (2) in which the needle (4) is exposed; and a plunger (10) rotationally and slidably disposed in the case (2), the plunger (10) rotatable relative to the case (2) between a first rotational position in which the plunger (10) is engaged to the case (2) and a second rotational position in which the plunger (10) disengages the case (2), wherein, the needle shroud (7) is operably coupled to the plunger (10), and wherein, when the needle shroud (7) translates from the first extended position (FEP) to the retracted position (RP), the plunger (10) rotates from the first rotational position to the second rotational position.
 2. The autoinjector (1) according to claim 1, wherein the needle shroud (7) is movable from the retracted position (RP) to a second extended position (SEP) relative to the case (2) in which the needle (4) is covered and the needle shroud (7) cannot translate relative to the case (2).
 3. The autoinjector (1) according to claim any one of the preceding claims, further comprising: a cap (11) removably coupled to the case (2).
 4. The autoinjector (1) according to claim 3, wherein the cap (11) includes an element adapted to engage a protective needle sheath (5) removably disposed on the needle (4).
 5. The autoinjector (1) according to claim 3, wherein the cap (11) includes at least one compliant beam (11.3) adapted to releasably engage at least one radial aperture (7.6) in the needle shroud (7).
 6. The autoinjector (1) according to claim 5, wherein, when the cap (11) is coupled to the case (2), the at least one compliant beam (11.3) engages the at least one radial aperture (7.6) in the needle shroud (7) and radially abuts the case (2).
 7. The autoinjector (1) according to claim 5, wherein, when the cap (11) is removed from the case (2), the at least one compliant beam (11.3) disengages the at least one radial aperture (7.6) in the needle shroud (7) and no longer radially abuts the case (2).
 8. The autoinjector (1) according to claim any one of the preceding claims, further comprising: a shroud spring (8) biasing the needle shroud (7) in a distal direction (D) relative to the case (2).
 9. The autoinjector (1) according to claim any one of the preceding claims, further comprising: a drive spring (9) biasing the plunger (10) in a distal direction (D) relative to the case (2).
 10. The autoinjector (1) according to claim 9, wherein the plunger (10) translates relative to the case (2) under force of the drive spring (9) when the plunger (10) is in the second rotational position and the needle shroud (7) is in the retracted position (RP).
 11. The autoinjector (1) according to claim 9, wherein the plunger (10) is at least partially hollow and the drive spring (9) is at least partially disposed within the plunger (10).
 12. The autoinjector (1) according to any one of claims 2 to 11, wherein the needle shroud (7) includes at least one compliant shroud beam (7.1) radially abutting the case (2) when the needle shroud (7) is in the first extended position (FEP) and the retracted position (RP), wherein the at least one compliant shroud beam (7.1) deflects radially when the needle shroud (7) is in the second extended position (SEP) and axially abuts the case (2).
 13. The autoinjector (1) according to any one of the preceding claims, wherien the plunger (10) includes a first plunger boss (10.1) adapted to engage a shroud rib (7.7) disposed on the needle shroud (7) and a second plunger boss (10.2) adapted to engage a case slot (2.3) in the case (2).
 14. The autoinjector (1) according to claim 13, wherein, when the plunger (10) is in the first rotational position and the needle shroud (7) is in the first extended position (FEP), the first plunger boss (10.1) engages the shroud rib (7.7) and the second plunger boss (10.2) engages the case slot (2.3).
 15. The autoinjector (1) according to claim 14, wherein, when the needle shroud (7) translates from the first extended position (FEP) to the retracted position (RP), the plunger (10) rotates from the first rotational position to the second rotational position and the second plunger boss (10.2) disengages the case slot (2.3).
 16. The autoinjector (1) according to claim 15, wherein the shroud rib (7.7) maintains the plunger (10) in the first rotational position when the needle shroud (7) is in the first extended position (FEP).
 17. The autoinjector (1) according to claim 16, wherein the needle shroud (7) includes a receiving element adapted to receive the first plunger boss (10.1) when the needle shroud (7) is in the retracted position (RP) and the plunger (10) is in the second rotational position.
 18. The autoinjector (1) according to claim 15, wherein, when the needle shroud (7) translates from the first extended position (FEP) to the retracted position (RP), the shroud rib (7.7) engages a plunger rib (10.3) to rotate the plunger (10) from the first rotational position to the second rotational position.
 19. The autoinjector (1) according to claim 15, wherein the plunger rib (10.3) is disposed at an angle relative to a longitudinal axis of the case (2). 